A paediatric form of myopathy with VCP deficiency

An international consortium of researchers has reported, for the first time ever, several paediatric cases of myopathy with a deficiency of VCP, a vasoline-containing protein previously implicated in an autosomal dominantEn génétique, c’est la caractéristique d’un individu qui n’a besoin que d’un seul exemplaire d’un certain gène (allèle) pour s’exprimer. Cet exemplaire unique peut venir du père ou de la mère. form of inclusion myopathy associated or not with Paget’s disease, motor neurone damage and frontotemporal dementia:

• 13 unrelated children were identified using the GeneMatcher programme,
• the clinical picture combined a developmental disorder, intellectual disability, hypotonia and macrocephaly,
• transmission was autosomal dominant with 13 mutations in the VCP gene, 12 of which were de novo,
• unlike the adult forms, functional studies showed that most of the missense variants had reduced ATPase activity.

This work significantly broadens the phenotypic spectrum of VCP deficiency.

An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP. Mah-Som AY, Daw J, Huynh D et al. Am J Hum Genet. 2023 Nov.